Acute lower respiratory tract disease is the leading contributor to morbidity and mortality in young children throughout the world. Respiratory syncytial virus (RSV) is the most important viral cause of serious lower respiratory tract disease in infants and children worldwide. It is also a significant cause of lower respiratory tract disease in the elderly and those with pre-existing chronic cardiac or lung disease such as cystic fibrosis (CF).
The structure and composition of RSV has been elucidated and is described in detail in the textbook “Fields Virology”, ed. by Knipe, D. M. et al., Lippincott Williams & Wilkins, NY (2001), in particular, Chapter 45, pp. 1443-1485, “Respiratory, Syncytial Virus” by Collins, P., Chanock, R. M. and Murphy, B. R.
RSV is an enveloped RNA virus of the family Paramyxoviridae and of the genus Pneumovirus. The two major protective antigens of RSV are the envelope fusion (F) and attachment (G) glycoproteins. The F protein is synthesized as a 68 kDa precursor molecule (F0) which is proteolytically cleaved into disulfide-linked F1 (about 48 kDa) and F2 (about 20 kDa) polypeptide fragments. The unglycosylated G protein (about 33 kDa) is heavily O-glycosylated giving rise to a glycoprotein of apparent molecular weight of about 90 kDa. Two broad subtypes of RSV have been defined A and B. The major antigenic differences between these subtypes are found in the G protein while the F protein is more conserved.
Currently, no immunogenic composition to prevent or attenuate RSV-related illness is available. Numerous candidate immunogenic compositions have been tested over the past thirty years but none have been licensed to date. First and second generations of the purified fusion protein (designated PFP-1 and PFP-2) immunogenic composition, an RSV subunit immunogenic composition, have been tested in RSV seropositive children and they have been shown to be safe and reasonably immunogenic.
The purification of the RSV F and G proteins by immunoprecipitation or preparative SDS-PAGE provides only small amounts of protein. Thus, there remains a need for immunogenic compositions effective in conferring protection against disease caused by RSV, and there is also a need for a process that produces high yields of the RSV glycoproteins to meet the demands of all target populations, such as older children and the elderly.